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“CADHERIN SWITCH” INITIATED BY ROYAL JELLY REGULATES MOTILITY OF COLORECTAL CANCER CELLS
* 1 , 2 , 2 , 3
1  Department for biology and ecology, Faculty of Science, University of Kragujevac, Kragujevac, 34000, Serbia
2  Institute for Information technologies, University of Kragujevac, Serbia
3  Institute for Information Technologies, University of Kragujevac, Serbia
Academic Editor: Antonios Koutelidakis

Abstract:

The basis of the negative reaction of colorectal cancer (CRC) to the application of certain treatment strategies is the acquisition of aggressive features during the process of epithelial–mesenchymal transition (EMT). It is known that the Wnt/β-catenin signal pathway is deregulated in CRC, and some specific markers are observed to be overexpressed in this disease, such as β-catenin transcription factor. Under the regulation of Wnt/β-catenin signaling appears the expression of the membrane proteins E-cadherin and N-cadherin, which are constitutive elements of intercellular junctions based on which the migration of cancer cells is controlled. Royal jelly (RJ) has already been recognized as a natural treatment with certain anti-cancer activities and antimetastatic potential, yet the exact molecular mechanism of these activities is still unknown.

This study aimed to assess the migratory potential of the colorectal cancer cell line SW-480 by applying the Transwell test, as well as to evaluate the expression of β-catenin, E-cadherin and N-cadherin at the gene level by using the qPCR method. Additionally, the E-cadherin and N-cadherin protein expression rates were determined by using immunofluorescence. All assays were carried out 24 h after treatment with RJ at two selected concentrations (10 and 100 μg/mL).

The results showed significant inhibition of SW-480 cells' migratory potential and downregulation of β-catenin gene expression after treatment with RJ. Concurrently, an increase in E-cadherin and the inhibition of N-cadherin at the protein level were induced by RJ at both applied concentrations. The difference in the SW-480 cells' responses to the two applied RJ concentrations was obvious, and the higher concentration (100 μg/mL) was more effective.

This study presents RJ as a promising therapeutic candidate for inhibiting the migratory potential of colorectal carcinoma cells by targeting regulatory and effector markers of EMT, thus offering potential avenues for modulating the aggressiveness of CRC.

Keywords: E-cadherin; EMT; Transwell; immunofluorescence; qPCR; N-cadherin
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